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NCT05877599PHASE1Recruiting

A Study of NT-175 in Adult Participants With Advanced Malignancies That Are Positive for HLA-A*02:01 and the TP53 R175H Mutation

AstraZeneca

Start Date

7/12/2023

Completion Date

7/31/2029

Summary

Phase I Study of NT-175, an autologous T cell therapy product genetically engineered to express an HLA-A\*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant malignancies

Detailed Description

This is a Phase 1, open-label, multicentre platform study to evaluate the safety and preliminary antitumour activity of NT-175 in HLA-A\*02:01 participants with advanced malignancies that are positive for the TP53 R175H mutation. Dose Escalation will investigate escalating doses of NT-175 in adult subjects with eligible histologies and will evaluate the safety and MTD and/or RDE/RP2D. Cohort expansion will further evaluate the safety and preliminary anti-tumour activity at or below the MTD in disease specific histologies and determine the RP2D. Dose Expansion will further evaluate the preliminary anti-tumour activity and safety of NT-175 at the RP2D in disease specific settings.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria (Module 1) * Subjects must be at least 18 years of age * Subject must be diagnosed with one of the histologies below: * NSCLC * Colorectal adenocarcinoma * HNSCC * Pancreatic adenocarcinoma * Breast cancer * Ovarian cancer * Any other solid tumor * Tumors must harbor a TP53 R175H variant mutation and subject must be HLA-A\*02:01 positive (at least 1 allele) * Subject has advanced solid cancer, defined as unresectable, advanced, and/or metastatic disease (Stage III or IV) after at least 1 line of approved systemic standard of care (SOC) treatment regimen and for which there are no available curative treatment options. * Subject has at least 1 measurable lesion * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * Adequate hematological, renal, hepatic, pulmonary, and cardiac function Key Exclusion Criteria (Module 1) * Any another primary malignancy within the 3 years prior to enrollment * Known, active primary central nervous system (CNS) malignancy * History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation. * History of clinically significant cardiac disease within the 6 months prior to enrollment or heart failure at any time prior to enrollment. * Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter, prior to enrollment. * Any form of primary immunodeficiency. * Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome. Key Inclusion Criteria (Module 2 - hematological malignancies) * At least 18 years of age * Diagnosis of AML or MDS that allows for efficacy assessments * Confirmation of TP53 R175H variant mutation in cancer cells * Subject must be HLA-A\*02:01 positive (at least 1 allele) * ECOG performance status of 0 to 1 Key Exclusion Criteria (Module 2 - hematological malignancy) * Acute promyelocytic leukaemia or isolated extramedullary disease * Another primary malignancy within 2 years (with exceptions) * HSCT within 100 days or immunosuppression for GvHD within 4 weeks * History of CNS or other extramedullary leukaemic involvement unless a lumbar puncture is negative for leukemic cells * Prior stroke, ischemic attack, significant cardiac disease, heart failure * Prior adoptive modified cell therapy * Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.

Interventions

BIOLOGICAL

NT-175

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Conditions

Non-small Cell Lung CancerHead and Neck Squamous Cell CarcinomaColorectal CarcinomaPancreatic AdenocarcinomaBreast CancerOther Solid TumorsOvarian CancerMyeloid Neoplasms (AML/MDS)

Locations

Research Site

Gilbert, Arizona 85234

United States

Research Site

Duarte, California 91010

United States

Research Site

Newport Beach, California 92663

United States

Research Site

Santa Monica, California 90404

United States

Research Site

Jacksonville, Florida 32224

United States

Research Site

Miami, Florida 33136

United States

Research Site

Tampa, Florida 33612

United States

Research Site

Boston, Massachusetts 02115

United States

Research Site

New Brunswick, New Jersey 08901

United States

Research Site

New York, New York 10065

United States

Research Site

Charlotte, North Carolina 28204

United States

Research Site

Winston-Salem, North Carolina 27103

United States

Research Site

Portland, Oregon 97213

United States

Research Site

Pittsburgh, Pennsylvania 15232

United States

Research Site

Nashville, Tennessee 37203

United States

Research Site

Houston, Texas 77030

United States

Research Site

Round Rock, Texas 78665

United States

Research Site

Milwaukee, Wisconsin 53226

United States